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The Fordyce Score

Scoring systems are useful to evaluate humans and animals.  The well known APGAR score is a test given to newborns soon after birth.  This test checks a baby’s heart rate, muscle tone, and other signs to see if extra medical care is needed.  The test is given at one minute after birth and again five minutes after birth. Another well known scoring system is the Mayhew Score, or more often the “Modified Mayhew Score”, that is intended to evaluate horses for equine protozoal myeloencephalitis.  The Mayhew Score differentiates upper motor neuron diseases from lower motor neuron diseases using an extensive neurological examination.  The scoring system allows the clinician to form a differential diagnosis list. Scoring systems are generally named for the author of the system.

The Fordyce Score is a system described by Fordyce, Edington, Bridges, Wright, and Edwards in 1987 that was designed to evaluate horses with cauda equina neuritis (polyneuritis equi, PNE) and differentiate PNE from other equine neuropathies by ELISA.

Polyneuritis equi is a condition with some specific characteristics that are paralysis of the tail, bladder, rectum and the anal and urethra sphincters, accompanied by an area of analgesia (loss of response to stimulus)  around the perineal region.  Muscle wasting is common over the hindquarters and the horse can have an uneven gait. Cranial nerves can be involved and characterized by a drooping lip and ears, inability to blink and atrophy of chewing muscles, although signs can involve other cranial nerves as well.

Because the pathology of PNE is inflammation of the nerve roots that form the cauda equina and any other peripheral nerves that are involved, it was common to examine affected nerves by histopathology.  Histopathology was used because horses were not diagnosed until late stage disease and euthanasia was the recommendation. The Fordyce team recognized that antibody against the animals own myelin protein could be measured pre-mortem using an ELISA test.  The first scientists to recognize that there were circulating antimyelin protein antibodies in experimental allergic neuritis in rats, was the Kadlubowski Group in 1980.  And in 1981, they recognized the same condition in horses with PNE.

Molecular techniques in the 1990’s allowed researchers to refine the antigens used to analyze serum samples.  This was important because laboratories that used a crude mix of myelin protein from horse spinal nerve tissues in their assays got varied results. The P2 myelin protein is the required  molecule and then it needs to be presented in its native form.  Rostami and Gregorian mapped the myelin P2 protein epitopes (short amino acid sequences that are reactive to the immune system) and showed that a small piece (peptide) of the protein caused an autoimmune reaction that appeared later in the course of disease.  The difference between the whole P2 protein antibody reaction and the peptide antibody reaction was that animals became refractory; they stopped responding to the epitopes on the whole P2 protein.  They stopped responding even when clinical disease was apparent.  Yet if the peptide was stimulating the animals’ immune system, they did not become refractory.

The animal isn’t a bystander in this disease.  The horse will heal the peripheral nerves because the cells that lay down more myelin (Schwann cells) are not compromised.  It is the degree of inflammation that can get out of control in late, irreversible disease.  In chronic disease the horse will heal (scar) the damaged nerves using fibrosis or calcium.  These healed nerves can’t conduct messages to the muscles that they innervate.  As the myelin is sequestered from the immune system the anti-myelin protein antibodies fade from disuse. This leaves the horse with end stage disease.  Thus there is a progression of anti P2 antibodies in the serum.  There will be no antibodies early in disease, as disease progresses antibodies are present, and finally, antibodies are absent in late disease due to the healing process.

Another IMG_0550reason for inconsistent assay results from some researchers was the selection of cases.  Because cases selected for study were end-stage it would not be expected that all horses would be seropositive on their ELISA assay.  A more uniform selection of cases can lend validity to the anti-myelin P2 serum assay and Fordyce was the first researcher to do this.  Fordyce clinically assessed animals for PNE giving one point to each of the following signs: tail paralysis, urine drippling, rectal dysfunction, perineal analgesia, muscle wastage over the hindquarters and any sign associated with a cranial nerve neuropathy, ear droop, inability to blink and masticatory muscle wastage (see picture). Fordyce considered a score of 4 or greater was consistent with PNE. Fordyce correlated 12 of 14 seropositive cases  (titer at 1 to 8) that were considered to have PNE based on clinical score and/or post mortem criteria .  These were gold standard cases. One horse had shivers and seroconverted to negative after 5 months. Thirteen horses with non-PNE neuropathies and 20 control negative sera were seronegative on the assay. Fordyce concluded that the presence of antibody to P2 in horses suffering from PNE is useful as a diagnostic for PNE.

We agree with Fordyce and have fine-tuned the anti-myelin protein P2 assay (MP2)  to include that small peptide (myelin protein 2 peptide, MPP) discovered a few years after his work was published. We believe that the value of a combined assay (MP2 and MPP) will allow us to measure the duration of the condition, if not the severity. The advantage to a diagnostic test is recognizing disease before it is late stage and irreversible. A diagnostic test will enable researchers to find effective treatments.  Let us know how you find the utility of the Fordyce Score system in your evaluation of equine neuropathies.  Call us to find out more about serum testing in these cases.